Previous cross-sectional and longitudinal studies performed on small numbers of subjects have implicated a few specific oral microorganisms such as B. gingivalis, B. intermedius, and A. (Haemophilus) actinomycetemcomitans, in the etiology of the different forms of human periodontal disease. Recent studies, suggest that 1.) only a small proportion of the population is infected with these pathogens; 2.) these microorganisms are transmissible among family members and; 3.) specific antigenic groups within these species may be particularly virulent. Consequently, we have formulated a new hypothesis on the nature of periodontal infections. We propose that periodontal disease develops secondary to subgingival infection with specific periodontal pathogens transmitted from an exogenous source, and that this infection constitutes a "risk factor" for periodontal disease. We propose to test this hypothesis by the following experimental approaches: First, determining the prevalence of periodontal pathogens in cross-sectional and longitudinal studies of a large adult sample using our recently developed species and serogroup- specific serodiagnostic reagents in rapid immunofluorescence assays and by DNA probe technology. Second, we will examine intrafamilial transmission of periodontal pathogens by molecular biological techniques including restriction fragment length polymorphism and by isozyme and antigenic analysis of bacterial isolates. Third, we will characterize the subgingival microflora in periodontitis patients with Acquired Immunodeficiency Syndrome by means of anaerobic culture in order to determine which microorganisms are important in the pathogenesis of their periodontal disease. Fourth, we will pursue serologic studies of the putative periodontal pathogens to pinpoint serogroups and corresponding antigens which are important in the etiology of human periodontal diseases. These studies will provide significant new information which will be useful in targeting high risk subjects for preventive therapy prior to the initiation of overt periodontal destruction.